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1 2020 Immunotherapy Side Effects Immune Checkpoint InhibitorsAvailable online at PATIENTS Please complete our online survey with support from: 1 nccn GUIDELINES for Patients Immunotherapy Side Effects: Immune Checkpoint inhibitors , 2020 Immune Checkpoint InhibitorsIt's easy to get lost in the cancer world 9 Step-by-step guides to the cancer care options likely to have the best results 9 Based on treatment GUIDELINES used by health care providers worldwide 9 Designed to help you discuss cancer treatment with your doctorsLet nccn GUIDELINES for Patients be your guide 2 nccn GUIDELINES for Patients Immunotherapy Side Effects: Immune Checkpoint inhibitors , 2020 AboutThese nccn GUIDELINES for Patients are based on the nccn GUIDELINES for Management of Immunotherapy Related Toxicities (Version , December 16, 2019).

2 2020 National Comprehensive Cancer Network, Inc. All rights reserved. nccn GUIDELINES for Patients and illustrations herein may not be reproduced in any form for any purpose without the express written permission of nccn . No one, including doctors or patients, may use the nccn GUIDELINES for Patients for any commercial purpose and may not claim, represent, or imply that the nccn GUIDELINES for Patients that have been modified in any manner are derived from, based on, related to, or arise out of the nccn GUIDELINES for Patients. The nccn GUIDELINES are a work in progress that may be redefined as often as new significant data become available. nccn makes no warranties of any kind whatsoever regarding its content, use, or application and disclaims any responsibility for its application or use in any Foundation seeks to support the millions of patients and their families affected by a cancer diagnosis by funding and distributing nccn GUIDELINES for Patients.

3 nccn Foundation is also committed to advancing cancer treatment by funding the nation s promising doctors at the center of innovation in cancer research. For more details and the full library of patient and caregiver resources, visit National Comprehensive Cancer Network ( nccn ) / nccn Foundation 3025 Chemical Road, Suite 100 Plymouth Meeting, PA 19462 GUIDELINES for Patients are developed by the National Comprehensive Cancer Network ( nccn )and supported by funding from nccn Foundation nccn 9 An alliance of leading cancer centers across the United States devoted to patient care, research, and educationCancer centers that are part of nccn : nccn GUIDELINES for Patients9 Present information from the nccn GUIDELINES in an easy-to-learn format9 For people with cancer and those who support them 9 Explain the cancer care options likely to have the best resultsFree online at nccn Clinical Practice GUIDELINES in Oncology ( nccn GUIDELINES ) 9 Developed by doctors from nccn cancer centers using the latest research and years of experience9 For providers of cancer care all over the world 9 Expert recommendations for cancer screening, diagnosis, and treatmentFree online at 3 nccn GUIDELINES for Patients Immunotherapy Side Effects.

4 Immune Checkpoint inhibitors , 2020 SupportersEndorsed byBe the Match National Marrow Donor Program (NMDP)/Be The Match is the global leader in providing a possible cure to patients with life-threatening blood and marrow cancers, as well as other diseases. Our Be The Match Patient Support Center provides support, information, and resources for patients, caregivers, and families. DaysGood Days is proud to support this educational resource for patients and their families and offers unwavering commitment to those who struggle with chronic disease, cancer, and other life-altering Cancer Stupid Cancer s mission is to empower adolescents and young adults affected by cancer by ending isolation and building community.

5 Through our innovative programming and strategic communications platforms, our goal is to provide support, resources, education, and a sense of community through online and in-person programming. Leukemia & Lymphoma SocietyThe Leukemia & Lymphoma Society (LLS) is dedicated to developing better outcomes for blood cancer patients and their families through research, education, support and advocacy and is happy to have this comprehensive resource available to patients. make a gift or learn more, Please visit or e-mail GUIDELINES for Patients Immunotherapy Side Effects: Immune Checkpoint inhibitors , 20205 nccn GUIDELINES for Patients Immunotherapy Side Effects: Immune Checkpoint inhibitors , 2020 Immune Checkpoint InhibitorsContents6 Checkpoint inhibitors and immune-related adverse events (irAEs)12 Skin irAEs19 Fatigue23 Gastrointestinal irAEs27 Endocrine irAEs33 Lung irAEs37 Musculoskeletal irAEs42 Less common irAEs51 Resources57 Words to know59 nccn Contributors60 nccn Cancer Centers61 Index6 nccn GUIDELINES for Patients Immunotherapy Side Effects.

6 Immune Checkpoint inhibitors , 202061 Checkpoint inhibitors and immune-related adverse events (irAEs)7 What are irAEs?9 Treatment with corticosteroids11 After a severe irAE11 Review7 nccn GUIDELINES for Patients Immunotherapy Side Effects: Immune Checkpoint inhibitors , 20201 Checkpoint inhibitors and irAEs What are irAEs?Immune checkpoint inhibitors have become the standard of care for some cancers. Like all cancer treatments, ICIs have side effects. A number of inflammatory reactions, or immune-related adverse events (irAEs), are possible. Immune checkpoint inhibitors (ICIs) are a type of immunotherapy. Immunotherapy is a modern approach to cancer treatment that harnesses the power of your own immune system to kill cancer cells.

7 Scientists have discovered different ways to use the immune system against cancer. In addition to ICIs, other types of immunotherapy include: CAR T-cell therapy Monoclonal antibodies Cancer vaccines Oncolytic virus therapyICIs are the focus of this patient guide. nccn GUIDELINES for Patients Immunotherapy Side Effects: CAR T-Cell Therapy is also available:The immune system s main job is to distinguish normal, healthy cells from abnormal cancer cells. Proteins on the surface of cancer cells PD-L1 for example interact with proteins on immune cells. These interactions are called immune checkpoints. The cancer cell proteins prevent attack by blindfolding the immune cells. ICIs remove the blindfold, allowing the immune system to see and attack cancer cells.

8 The two main types of ICIs currently used for cancer immunotherapy are: PD-1/PD-L1 inhibitors The CTLA-4 inhibitor ipilimumab (Yervoy )PD-1 inhibitors include: Cemiplimab (Libtayo ) Nivolumab (Opdivo ) Pembrolizumab (Keytruda )PD-L1 inhibitors include: Atezolizumab (Tecentriq ) Avelumab (Bavencio ) Durvalumab (Imfinzi )What are irAEs? Boosting the immune system with immunotherapy can cause your immune cells to attack healthy cells in the body. This results in inflammation and side effects known as immune-related adverse events (irAEs). These side effects are similar to those of autoimmune disorders, in which the immune system sees healthy cells as a threat and attacks them. 8 nccn GUIDELINES for Patients Immunotherapy Side Effects: Immune Checkpoint inhibitors , 20201 Checkpoint inhibitors and irAEs What are irAEs?

9 Immune-related side effects can range from mild to life-threatening. They can occur at any time during or even after treatment is over, and may affect one or more organ systems. Some side effects may worsen over the course of treatment, with each dose of immunotherapy. Most irAEs can be managed effectively if found and treated early. The side effects of ICI therapy are generally more severe when being treated with both a CTLA-4 inhibitor and a PD-1/PD-L1 inhibitor. How common are irAEs?Inflammatory skin conditions are the most common side effects of ICI therapy. Rash and itching are very common. Blisters may be a sign of a rare and severe blistering disorder. Fatigue is also very common, followed by diarrhea and inflammation of the large intestine (colitis).

10 ICIs can also cause inflammation of the thyroid, pituitary, and adrenal glands. These hormone-related, or endocrine, irAEs are somewhat common. Inflammation of the lungs (pneumonitis) is also possible, but does not always cause symptoms. Musculosketal, or rheumatic, irAEs are less common. They include inflammatory forms of arthritis and muscle pain and inflammation. Rare but potentially severe side effects include those affecting the nervous system, kidneys, pancreas, heart, and for irAEsDuring ICI therapy it is important to stay in close contact with the center where you are receiving treatment. Symptoms that may seem unrelated (diarrhea and shortness of breath, for example) may be signs of an irAE. Notify all of your health care providers (especially your primary care doctor), that you are receiving, or have received, immunotherapy.